Drugs Xagena
The U.S. Food and Drug Administration ( FDA ) has approved Talzenna ( Talazoparib ), an oral poly ADP-ribose polymerase ( PARP ) inhibitor, in combination with Enzalutamide ( Xtandi ), for the treatment of adult patients with homologous recombination repair ( HRR ) gene-mutated metastatic castration-resistant prostate cancer ( mCRPC ).
This approval is based on the statistically significant and clinically meaningful radiographic progression-free survival ( rPFS ) data from the phase 3 TALAPRO-2 trial, which has demonstrated a 55% reduction in the risk of disease progression or death in patients with metastatic castration-resistant prostate cancer with prospectively identified HRR gene mutations ( ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C ) treated with Talazoparib plus Enzalutamide versus placebo plus Enzalutamide ( hazard ratio, HR 0.45; 95% CI, 0.33–0.61; p less than 0.0001 ).
Metastatic castration-resistant prostate cancer is a form of prostate cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone.
Approximately 10-20% of patients with prostate cancer develop metastatic castration-resistant prostate cancer within 5-7 years of diagnosis, and in the U.S. in 2020, approximately 60-90 thousand of the three million cases of prostate cancer were metastatic castration-resistant prostate cancer.
HRR gene mutations are found in approximately 25% of tumors from men with metastatic castration-resistant prostate cancer and have been associated with aggressive disease and poor prognosis.
The phase 3 TALAPRO-2 trial is a two-part, two-cohort, multicenter, randomized, double-blind, placebo-controlled study that included two patient cohorts: Cohort 1 ( all-comers; n=805 ) and Cohort 2 ( those with HRR mutations [ HRRm ]; n=399 ).
The primary endpoint of the trial was radiographic progression-free survival, and overall survival ( OS ) was a key secondary endpoint.
The results from the TALAPRO-2 Cohort 1 were previously reported and published in The Lancet. A trend in overall survival favoring Talazoparib plus Enzalutamide was also observed, though these data are immature.
The safety of Talazoparib plus Enzalutamide in the TALAPRO-2 trial was generally consistent with the known safety profile of each medicine. Serious adverse reactions occurred in 30% of patients treated with Talazoparib plus Enzalutamide. Serious adverse reactions reported in more than 2% of patients included anemia ( 9% ) and fracture ( 3% ).
Discontinuation of Talazoparib occurred in 10% of patients.
Talazoparib is an oral inhibitor of PARP, which plays a role in DNA damage repair. Preclinical studies have demonstrated that Talazoparib blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death.
Talzenna indication in the U.S.
Talzenna is indicated for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene ( BRCA )-mutated ( gBRCAm ) HER2-negative locally advanced or metastatic breast cancer. The patients must be selected for therapy based on an FDA-approved companion diagnostic for Talzenna.
Talzenna is indicated in combination with Enzalutamide for the treatment of adult patients with HRR gene-mutated metastatic castration-resistant prostate cancer. ( Xagena )
Source: Pfizer, 2023
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